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This Article Full Text Full Text (PDF) All Versions of this Article: 296/5/R1385    most recent 90411.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Griol-Charhbili, V. Articles by Richer, C. Search for Related Content PubMed PubMed Citation Articles by Griol-Charhbili, V. Articles by Richer, C.

HEMODYNAMICS AND CARDIORENAL INTEGRATION

Tissue kallikrein deficiency and renovascular hypertension in the mouse

¹INSERM U872, Centre de Recherche des Cordeliers, Paris; ²Paris Descartes University, Paris; ³INSERM U633, Hôpital Broussais, Paris; ⁴Asistance Publique, Hôpitaux de Paris;⁵ Université Paris-Sud, Le Kremlin-Bicêtre, France

Submitted 7 May 2008 ; accepted in final form 13 February 2009

The kallikrein kinin system (KKS) is involved in arterial and renal functions. It may have an antihypertensive effect in both essential and secondary forms of hypertension. The role of the KKS in the development of two-kidneys, one-clip (2K1C) hypertension, a high-renin model, was investigated in mice rendered deficient in tissue kallikrein (TK) and kinins by TK gene inactivation (TK–/–) and in their wild-type littermates (TK+/+). Four weeks after clipping the renal artery, blood flow was reduced in the clipped kidney (2K1C-TK+/+: –90%, 2K1C-TK–/–: –93% vs. sham-operated mice), and the kidney mass had also decreased (2K1C-TK+/+: –65%, 2K1C-TK–/–: –66%), whereas in the unclipped kidney, blood flow (2K1C-TK+/+: +19%, 2K1C-TK–/–: +17%) and kidney mass (2K1C-TK+/+: +32%, 2K1C-TK–/–: +30%) had both increased. The plasma renin concentration (2K1C-TK+/+: +78%, 2K1C-TK–/–: +65%) and renal renin content of the clipped kidney (2K1C-TK+/+: +58%, 2K1C-TK–/–: +65%) had increased significantly. There was no difference for these parameters between 2K1C-TK+/+ and 2K1C-TK–/– mice. Blood pressure monitored by telemetry and by plethysmography, rose immediately after clipping in both genotypes, and reached similar levels (2K1C-TK+/+: +24%, 2K1C-TK–/–: +21%). 2K1C-TK+/+ and 2K1C-TK–/– mice developed similar concentric left ventricular hypertrophy (+24% and +17%, respectively) with normal cardiac function. These findings suggest that in the context of chronic unilateral reduction in renal blood flow, TK and kinins do not influence the trophicity of kidneys, the synthesis and secretion of renin, blood pressure increase, and cardiac remodeling due to renin angiotensin system activation.

kallikrein kinin system; renin-angiotensin system; mice